1. Field of the Invention
The invention relates to the field of packaging biopharmaceutical fluids, and it relates more specially to a rigid container for a flexible 3D (three-dimensional) pouch, designed to contain such a biopharmaceutical fluid, a flexible 3D pouch that is designed for such a container, and a process for implementation of such a container.
2. Description of the Related Art
“Biopharmaceutical product” is defined as a product that is obtained from biotechnology—culture media, cellular cultures, buffer solutions, artificial nutrition liquids, blood products, and derivatives of blood products—or a pharmaceutical product or more generally a product that is designed to be used in the medical field. Such a product is in liquid, pasty or optionally powder form. The invention also applies to products that are different but that are subject to analogous requirements as regards their packaging.
A 3D pouch is known that is designed to accommodate such a biopharmaceutical product, which comprises a lower end wall, an upper end wall, and a flexible side wall that can be in two end states—folded flat and deployed unfolded—and can be deformed to switch from one to the other of these states or to be in any intermediate state. The walls of the pouch, made of a plastic material such as polyethylene or a complex that comprises polyethylene, delimit an inner space that, in the folded state, has a minimum volume, and, in the unfolded and deployed state, has a maximum volume. This space is designed to accommodate the biopharmaceutical product for storage, treatment, and monitoring. Such a disposable, biocompatible, flexible pouch can have a large volume of at least 50 liters up to 3,000 liters and even more, which justifies the fact that it is described as 3D. Such a pouch thus offers a large capacity while being able to be easily stored. An example of such a pouch is described in the International Application WO00/04131.
Such a flexible 3D pouch, when it is filled with biopharmaceutical product, is to be placed in a rigid container that holds it by the outside. This requirement is most particularly important in the case where the pouch that is filled with biopharmaceutical product is to be shipped and transported by road, train, or by air. Actually, there is then the risk that the integrity of the pouch is affected as a result of impacts, forces, deformations . . . which can in turn affect the biopharmaceutical product that it contains.
In one embodiment, such a rigid container comprises a lower transverse wall and an erect side peripheral axial wall that limits an upper transverse opening with access to a housing that is defined by the inner surfaces of these walls and is able to accommodate the pouch that contains the biopharmaceutical fluid that was just applied against these inner surfaces.
The document EP-A-1012073 describes such a container, also equipped with a wall for protection and containment that can be placed transversely in the housing of the rigid container, having dimensions such that the transverse gap between its outside peripheral free edge and the inner surface of the side wall opposite the rigid container is limited. Such a wall for protection and containment is able to be applied with a certain axial force against the outside surface of the upper end wall of the pouch and to be held fixed in this position by holding means in the active state, resting via a screw cylinder system on removable spars located in this case in the upper part of the rigid container.
With the arrangement according to the document EP-A-1012073, the axial space requirement in height of the cylinder system determines the travel in height at which the plate for protection and containment can be located. Either this space requirement is selected to be limited, for the advantages that this provides, with the drawback that the plate for protection and containment can be used only with a completely filled pouch, or, if it is desired that the travel of the containment plate be as great as possible, for example because the pouch could be only partially filled, the cylinder system necessarily has a large axial space requirement in height, which is a source of problems, the lack of compactness being a serious handicap for shipping and transport.
Actually, since the flexible pouch has a large maximum capacity and in view of the very nature of its contents—a biopharmaceutical product—it should be possible to use the pouch continuously without having to fill it completely, and with variable volumes. However, this situation poses another problem when the flexible pouch that is partially filled with biopharmaceutical product is to be shipped and transported, primarily over a significant distance and under conditions such that it is prone to abrupt movements or to significant accelerations, because the high inertia of the contents of the flexible pouch then creates a movement of imbalance of the pouch and its contents that can affect the integrity of the pouch and therefore of its contents.
The document WO 2006/070010 describes a process for packaging a viscous product that is contained in a flexible pouch with a capacity that is greater than 50 liters, preferably greater than 100 liters, in volume units with a capacity of less than 50 liters, preferably less than 100 liters. This flexible pouch comprises a passage for evacuation of the viscous product located on its upper end wall. This flexible pouch, filled with viscous product, is placed in a rigid container that has a lower transverse wall that forms a pressure piston, mounted to slide vertically and driven by a cylinder system placed below this lower transverse wall and above a stationary lower floor. This container further comprises a stationary upper cover that is reversible and is equipped with an opening for sending the viscous product to a packaging machine in a smaller volume, in communication with the passage for evacuation of the flexible pouch. By deploying the cylinder, the lower transverse wall is moved upward, and the flexible pouch is compressed between this wall and the cover, which makes it possible to expel the viscous product from the flexible pouch for sending it to the packaging machine.
The goal of the arrangement according to the document WO 2006/070010 is to produce viscous products, but not biopharmaceutical products. It does not have the objective of preserving the integrity of the pouch and its contents, and its goal is not the case of a pouch that is partially filled with its contents being able to be shipped and transported over a significant distance and/or under conditions that are suitable for generating abrupt movements or significant accelerations. This arrangement is not concerned, moreover, with the compactness of the rigid container. Finally, this arrangement imposes an evacuation at the top, whereas in the case of 3D pouches for biopharmaceutical products, the evacuation is most often at the bottom. In the arrangement according to the document WO 2004/074164, this drawback is eliminated, but not the others, in particular the lack of compactness. Analogous devices are described in the documents GB-A-2159583 and BE-A-539623.
Also known from the document FR-A-0 932 321 is a container that comprises, on the one hand, a tank inside of which an envelope is placed, and, on the other hand, a holding plate that rests on the envelope when the latter is not completely filled or its size in height is less than that of the tank. The holding plate is then held inside the tank by means of a pressure screw working with threaded recesses arranged in the inside wall of the tank, as shown in FIG. 4 of this document.
One drawback of this device is that it does not make it possible to preserve the integrity of the envelope regardless of its filling volume. Actually, the position of the holding plate necessarily depends on the position of the threaded recesses. Consequently, the position of this holding plate with respect to the bottom of the tank cannot be modulated continuously because of the filling of the envelope.
Also known from the state of the art is the document EP-A-0 456 403 that discloses a container for a flexible pouch that is filled with a pharmaceutical product. According to this embodiment, a support element is attached to the upper surface of the flexible pouch so as to move this upper surface to the same level as the product when a portion of this product flows from the flexible pouch.
Such an embodiment has, like the preceding embodiments, several drawbacks. In particular, the use of a support element is inadequate for preventing the pharmaceutical product that is contained in the flexible pouch from sloshing inside the latter when the container is put into motion. Actually, the weight alone of the support element does not provide an adequate holding force to counter the forces exerted on the flexible pouch when the product that it contains is put into motion and moves about.
There is therefore a need for a rigid container for a large-capacity flexible 3D pouch that, on the one hand, is able to preserve the integrity of the pouch and its contents, even when the pouch is only partially filled with biopharmaceutical product, when the thus filled pouch is shipped and transported over a significant distance and/or under conditions suitable for generating abrupt movements or significant accelerations, and that, on the other hand, is compact.